The invention is directed to a system for the controlled and sustained delivery of therapeutic agents to the human bladder.
There are numerous conditions of the bladder or urinary tract, such as cancer, inflammation, infection or incontinence, that may be treated by pharmaceutically active compounds. Many of these compounds are presently orally administered, however, that is a disadvantage in that systemic delivery is used to treat a condition or disease that is possibly more effectively treated by local applications. Also, many of the drugs used for the treatment of urge incontinence are anti-cholinergics with potent adverse side effects. An intravesical administration would accomplish a high concentration of the drug locally in the bladder wall or urine without producing a high serum concentration.
The following are some typical or currently used intravesical treatments of the bladder. For the treatment of bladder cancer, the drug doxorubicin is instilled directly into the bladder. A mycobacterium, Bacillus Calmette-Guerin, is also administered intravesically for treatment of carcinoma located in the bladder. For interstitial cystitis, DMSO is instilled intravesically to provide symptomatic relief. For incontinence, the anticholinergic drug oxybutynin chloride has been reported to have been used.
In these cases of intravesical delivery, the drug is simply instilled by solution into the bladder. A disadvantage with this approach is that for chronic conditions such as incontinence, the patient must be repeatedly catheterized, thus requiring frequent attention by trained medical staff. Also, the potential for infection is increased by repeated catheterization into the bladder, which can be as often as several times per day.
Okado et al., Yakugaku Zasshi, 105(10), 1001-1003 (1985); Nichihitsunyokaishi, 76(2), 197-203 (1985); tested an intravesical stick made of beeswax and surfactants, incorporating the drug bleomycin. However, it was observed that elution of the drug from the stick was rather rapid, about 1 to 3 days, and particles of the stick remain in the bladder, which could lead to blockage of the urinary tract or to the formation of kernels for bladder stones.
Accordingly, it would be desirable to provide a sustained or controlled delivery device that is capable of delivery of the drug for an extended period of time, preferably one week or longer, with the device biodegrading or bioeroding over time to clear the bladder.
The invention provides a bioerodible, sustained-release preparation for placement into the bladder through the urethra. The preparation may have a specific gravity less than or equal to that of the specific gravity range of human urine. The preparation comprises a pharmaceutically active ingredient and at least one bioerodible, pharmaceutically acceptable carrier, which is capable of sustaining delivery of the active ingredient within the bladder and is bioerodible and excretable without blockage of the urinary tract.